Wang Jing-Zhong, Fang Yan, Ji Wei-Dong, Xu Hui
Department of Neurology, The First People's Hospital of Shangqiu City, No 292, South Kaixuan Rd., Shangqiu 476100, Henan, People's Republic of China.
Department of Neurology, The First People's Hospital of Shangqiu City, No 292, South Kaixuan Rd., Shangqiu 476100, Henan, People's Republic of China.
Biochem Biophys Res Commun. 2017 Jan 29;483(1):216-222. doi: 10.1016/j.bbrc.2016.12.163. Epub 2016 Dec 26.
The liver X receptors (LXRs) are transcriptional regulators of lipid homeostasis and may be critical for neurodegeneration and neurogenesis in vivo. However, it remains largely unknown about the role of LXRs and its agonists in the in vitro proliferation of neural progenitor cells (NPCs). Here we revealed for the first time that LXRs were markedly expressed in mouse NPCs and were critical for the in vitro proliferation. LXR agonists GW3965 and LXR623 promoted the proliferation of wildtype NPCs, but not NPCs from LXR double-knockout mice. Mechanistically, phosphorylation of MEK1/2 and ERK1/2 in NPCs was enhanced upon LXR agonist treatment, while abrogation of MEK/ERK phosphorylation by the inhibitors PD98059 and U0126 impaired the proliferation of wildtype NPCs in the presence or absence of LXR agonists. Collectively, our findings suggest that LXR agonists GW3965 and LXR623 can stimulate the NPC proliferation in LXR- and MEK/ERK-dependent manner.
肝脏X受体（LXRs）是脂质稳态的转录调节因子，在体内对神经退行性变和神经发生可能至关重要。然而，LXRs及其激动剂在神经祖细胞（NPCs）体外增殖中的作用在很大程度上仍不清楚。在此，我们首次揭示LXRs在小鼠NPCs中显著表达，并且对体外增殖至关重要。LXR激动剂GW3965和LXR623促进野生型NPCs的增殖，但对LXR双敲除小鼠来源的NPCs无此作用。机制上，LXR激动剂处理后NPCs中MEK1/2和ERK1/2的磷酸化增强，而抑制剂PD98059和U0126消除MEK/ERK磷酸化会损害野生型NPCs在有无LXR激动剂情况下的增殖。总之，我们的研究结果表明，LXR激动剂GW3965和LXR623可以通过依赖LXR和MEK/ERK的方式刺激NPCs增殖。
